Role of Lipid Charge in Organization of Water/Lipid Bilayer Interface: Insights via Computer Simulations

Anionic unsaturated lipid bilayers represent suitable model systems that mimic real cell membranes:  they
are fluid and possess a negative surface charge. Understanding of detailed molecular organization of water−lipid interfaces in such systems may provide an important insight into the mechanisms of proteins' binding
to membranes. Molecular dynamics (MD) of full-atom hydrated lipid bilayers is one of the most powerful
tools to address this problem in silico. Unfortunately, wide application of computational methods for such
systems is limited by serious technical problems. They are mainly related to correct treatment of long-range
electrostatic effects. In this study a physically reliable model of an anionic unsaturated bilayer of 1,2-dioleoyl-sn-glycero-3-phosphoserine (DOPS) was elaborated and subjected to long-term MD simulations. Electrostatic
interactions were treated with two different algorithms:  spherical cutoff function and particle-mesh Ewald
summation (PME). To understand the role of lipid charge in the system behavior, similar calculations were
also carried out for zwitterionic bilayer composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). It
was shown that, for the charged DOPS bilayer, the PME protocol performs much better than the cutoff scheme.
In the last case a number of artifacts in the structural organization of the bilayer were observed. All of them
were attributed to inadequate treatment of electrostatic interactions of lipid headgroups with counterions.
Electrostatic properties, along with structural and dynamic parameters, of both lipid bilayers were investigated.
Comparative analysis of the MD data reveals that the water−lipid interface of the DOPC bilayer is looser
than that for DOPS. This makes possible deeper penetration of water molecules inside the zwitterionic (DOPC)
bilayer, where they strongly interact with carbonyls of lipids. This can lead to thickening of the membrane
interface in zwitterionic as compared to negatively charged bilayers.